This invention relates to an ocular drug dispensing device for administering a drug to the eye at a controlled and continuous dosage rate.
One of the first ocular devices for dispensing drugs directly to the eye consisted of a lamella of a drug dissolved or dispersed in a water-soluble gel of glycerinated gelatin that was applied to the inner surface of the eyelid. The glycerinated gelatin dissolved rapidly in tear fluid with an accompanying quick release of drug to produce the same kind of effect as liquid dosage forms such as eye drops or ointments. Such lamellae do not provide sustained dispensing and they are not generally used in ophthalmic therapy. See Remington's Pharmaceutical Sciences, Ed. XIII, pages 547 to 548, 1965, published by Mack Publishing Co., Easton, Pa., and An Introduction to Pharmaceutical Formulation, by Fishburn, page 116, 1965, published by Pergamon Press, Ltd., New York, N.Y.
Recent advances for administering a drug to the eye are disclosed in U.S. Pat. Nos. 3,416,630 and 3,618,604 owned by Applicant. These patents describe ocular inserts that act as a depot or drug reservoir for slowly releasing drug to the eye for prolonged periods of time. The inserts are fabricated of flexible polymeric materials that are biologically inert, non-allergenic, and insoluble in tear fluid. To initiate the therapeutic program, these ocular inserts are placed in the cul-de-sac between the sclera of the eyeball and the eyelid for administering drug to the eye. Since the ocular inserts are formed of polymeric materials that are insoluble in tear fluid, they retain their shape and integrity during the course of the needed therapy to serve as a drug reservoir for continuously administering drug to the eye and the surrounding tissues at a rate that is not affected by dissolution or erosion of the polymeric material. The ocular insert, on termination of the desired therapeutic program, is removed from the cul-de-sac. Thus, the inserts of the above-mentioned patents provide a complete ophthalmic dosage regime for a prolonged period of time, generally on the order of 24 hours or longer.
The device of U.S. Pat. No. 3,416,530 is manufactured with a plurality of capillary openings that communicate between the exterior of the device and an interior chamber generally defined from a polymeric membrane. While these capillary openings and this construction are effective for releasing drug to the eye, they add considerable complexity to the manufacture of the device because it is difficult to control the size of these openings in large scale manufacturing using various polymers as required for various drugs.
The device of U.S. Pat. No. 3,618,604 does not involve such capillary openings, but instead provides for the release of drug by diffusion through a polymeric membrane at a drug release rate that can be controlled with precision and reproducibility. The device, in a preferred embodiment, as disclosed in that patent, comprises a sealed container having the drug in an interior chamber. While remarkably effective for administering drug, certain problems have been encountered in manufacturing the devices. For example, one problem is the difficult task of sealing the margins of the membrane to form the container. Another problem met in making such device when drug in solid form is contained therein, is the stresses and strains introduced into the membrane walls from deformation during manufacture in forming the reservoir, causing the device, in many instances, to rupture and leak. In addition, this causes entrappment of air and the alteration of the release characteristics of the membrane. A further problem with such devices when used for containing drug in liquid form, is that during manufacture, the liquid spreads and wets the sealable surfaces. These wet surfaces cannot be sealed to make a device essentially free of leaks.